蛋白酶抑制剂MG132对肿瘤细胞的生长抑制作用研究  

MG132 as a proteasome inhibitor induces cell growth inhibition in human cancer cells

作　　者：王天晓[1] 王颖莹[1] 张中庆[1] 

机构地区：[1]河南大学中药研究所/河南大学药学院,开封475004

出　　处：《中国医疗前沿》2012年第19期10-12,共3页China Healthcare Innovation

摘　　要：目的探讨MG132对人类肿瘤细胞U2OS、HepG2和MCF7的生长抑制作用及机制。方法 MTS法检测MG132对肿瘤细胞生长的影响;化学/荧光发光法检测MG132对细胞内O2-及ROS含量的影响;谷胱甘肽检测试剂盒检测细胞内GSH水平变化;Western blot检测MG132对核转录因子Nrf2及γ-谷氨酰半胱氨酸合成酶γ-GCS表达的影响,探索MG132的抗肿瘤作用机制。结果 MG132可剂量依赖性地抑制U2OS、HepG2和MCF7细胞的生长,其IC50值分别为3μM、3μM和2μM;MG132可升高细胞内ROS水平,降低细胞内GSH水平;同时MG132降低了Nrf2及γ-GCS的表达。结论蛋白酶抑制剂MG132对U2OS、HepG2和MCF7细胞的生长具有抑制作用,其可能通过抑制Nrf2及γ-GCS的表达来降低细胞内的GSH水平,从而发挥其抗肿瘤作用。Objective To investigate the inhibitory effect and mechanism of MG132（Carbobenzoxy-Leu-Leu-leucinal） on U2OS, HepG2 and MCF7 cells. Methods MTS assay was used to detemine the inhibitory rate of MG132 on cancer cells. Fluorescence probe method were performed to detect the leve of 02- and ROS. Intracellular glutathione（GSH） content was tested by the OxiSelectTM Total Glutathione（GSSG/GSH） Assay Kit. Western blot determined the effect of MG132 on expression of Nrf2 and γ-GCS. Results Treatment with MG132 inhibited the growth of U2OS, HepG2 and MCF7 cells with an ICs0 of approximately 3μM, 3μM and 2μM respectively at 24h. The intracellular ROS levels including 02 were dose-dependently increased in MG132-treated cells. MG132 induced GSH depletion in U2OS, HepG2 and MCF7 cells at a dose dependent maimer. In addition, 2μM MG132 decreased the expression of Nrf2 and γ-GCS. Conclusion MG132 inhibited the growth of human cancer U2OS, HepG2 and MCF7 cells via inducing the changes of ROS and GSH levels and inhibition of expression of Nrf2 and γ-GCS. Our present data provide important information on the anti-growth mechanisms of MG132 in human cancer U2OS, HepG2 and MCF7 cells in relation to GSH and Nrf2/γ-GCS.

关 键 词：蛋白酶抑制剂 肿瘤 还原型谷胱甘肽 NRF2 Γ-GCS 

分 类 号：R392.1[医药卫生—免疫学]